The present invention relates to techniques for chemical analysis in a capillary, and more particularly to techniques for chemical analysis in a microchannel requiring interfacing with liquid reservoirs for supplying chemical reagents to the microchannel.
In the instrumentation of sample chemical analysis, and especially in separation systems such as gas chromatography (GC), liquid chromatography (LC), and capillary electrophoresis (CE) systems, smaller dimensions will generally result in improved performance characteristics and at the same time result in reduced production cost and analysis cost. In this regard, miniaturized separation systems provide more effective system design, result in lower overhead due to decreased instrumentation sizing, and, additionally, enable increased speed of analysis, decreased sample and solvent consumption and the possibility of increased detection efficiency and probability.
In the design of columnar analytical systems, e.g., LC and GC, the total column volume and total column length are made such that different parts of the analytical system can be connected by the column instead of using transfer lines. Nowadays, in CE, the total column length and total column volume are greatly reduced compared to earlier devices. For the modern CE equipment, connectors become less common but specialty fittings frequently are still needed. The column is still required to have sufficient length to pass from an injector through a temperature-controlled area to the point of detection.
Recently, planar column devices have been developed for chemical analysis. Examples are U.S. Pat. Nos. 5,658,413 (Kaltenbach et al.); 5,645,702 (Witt et al.); 5,641,400 (Kaltenbach et al.); 5,500,071 (Kaltenbach et al.); and 5,571,410 (Swedberg et al.), said patents are incorporated by reference in entirety herein. These devices are quite small, having sizes from a fraction of a centimeter to a few centimeters. In such a device, in addition to a separation compartment (which is a channel), there are usually other compartments for sample handling and preparation before or after the separation step. The advantage of such planar column devices is the ease of integrating different functionality in a single device. However, for such small devices, the total volume is so small that no standard connections can be used to connect these devices to transfer lines. Attempts in using transfer lines for connection will add significantly to the overall volume and therefore adversely affect the separation efficiency. The instrumentation of such small devices presents a challenge. Instead of bringing and connecting a long and relatively large column to different parts of a station, which may have liquid reservoirs, power supply, heating-cooling mechanisms, and other electronic or mechanical parts as in conventional equipment, in making equipment using the planar columns, the instrumentation has to be adapted to interface with the small planar column device. In other words, the various parts of the chemical analysis equipment for instrumentation have to be brought close together in a compact space to interface with such a small device. What is needed is a technique for such compact instrumentation.
In one aspect, this invention provides modular microchannel apparatuses for the analysis of analyte. In one such apparatus, there is a separation unit and a reservoir unit. When modularly coupled together, the apparatus can be used for chemical analysis. The separation unit includes a microchannel, in which the analyte can be driven to pass through the microchannel according to the molecular characteristics of the analyte. The time for the analyte to pass through the microchannel is indicative of the molecular characteristics of the analyte. The reservoir unit has one or more reservoirs for coupling operatively modularly with the separation unit to supply to it liquid reagents. The reservoirs have prepackaged liquid reagents stored in them before the reservoir unit is coupled with the separation unit.
One advantage of such modular apparatuses is that the individual parts that are to be modularly coupled can be manufactured separately, shipped, and handled separately before assembly for use. Furthermore a wide variety of different parts can be made such that a skilled person can pick and choose among them for the particular application of interest. For example, the skilled person may choose a separation unit with a microchannel of a particular length and size for the analysis of a particular sample and choose a separation unit with a microchannel of a different length and size for a different sample, but choose the same reservoir unit, power unit, heating unit, etc. for the analysis of both samples. Furthermore, the compact design of the modularly coupled apparatus of the present invention greatly reduces the need for connectors and adaptors that traditionally are used to join the analytical columns, detection units, power supply, pressure units, flushing fluid supply, buffer solutions supply, and the like. This compact design allows the analytical operator tremendous flexibility which significantly reduce the burden of carrying a large number of adaptors, connectors, or even whole sets of equipment as in prior technology. The present equipment and technique of analysis can be applied in many chemical and biochemical analyses that are done with traditional analytical techniques using columns, including analyzing chemical, biochemical, and biological samples, including those mentioned in the aforementioned Kaltenbach et al., Witt et al., and Swedberg et al. patents.